Cargnel Antonietta, Angeli Elena, Mainini Annalisa, Gubertini Guido, Giorgi Riccardo, Schiavini Monica, Duca Piergiorgio
II Department Infectious Diseases, Luigi Sacco Hospital, Milan, Italy.
Antivir Ther. 2005;10(2):309-17.
Chronic hepatitis C is common and aggressive in HIV-positive patients, so the development of a well-tolerated HCV therapy is a priority. We evaluated the efficacy and safety of pegylated interferon alpha2b (PEG-IFN) plus ribavirin (RBV) versus PEG-IFN monotherapy in HIV/HCV-coinfected patients undergoing highly active antiretroviral therapy (HAART), and analysed the predictive factors of response.
An Italian, multicentre, open-label trial including 135 coinfected patients, randomized to PEG-IFN 1.5 microg/kg/week plus RBV 400 mg twice daily (n=69, arm A) or PEG-IFN 1.5 microg/kg/week (n=66, arm B) for 48 weeks. We assessed the predictive values of early virological response (EVR) at week 8 (HCV-RNA drop >2 log10 compared with baseline or undetectable levels) on sustained virological response (SVR).
Fifty-five patients (28 from arm A and 27 from arm B) completed 48 weeks of therapy. At the end of treatment, 20/28 patients in arm A and 11/27 in arm B had HCV-RNA <50 IU/ml. In a per-protocol analysis, SVR was reached by 54% of patients in arm A (genotype 2-3, 11/16; genotype 1-4, 4/12) and 22% in arm B (genotype 2-3, 3/15; genotype 1-4, 3/12). In an intention-to-treat analysis, the SVR was 22% in arm A (genotype 2-3, 11/32; genotype 1-4, 4/37) versus 9% in arm B (genotype 2-3, 3/32; genotype 1-4, 3/34). The best predictors of SVR were the use of combination therapy, infection with HCV genotype 3 versus genotype 1, and EVR at week 8. Thirty patients (15 from arm A and 15 from arm B) dropped out of the trial prematurely due to side effects. The positive predictive value of EVR at week 8 was 65%, the negative predictive value was 86%.
PEG-IFN plus RBV can be considered a solid option for the treatment of HIV/HCV-coinfected patients. The key to successfully improving efficacy is strong compliance through strict overall patient monitoring, in order to best manage drug toxicity. EVR assessment at week 8 may become a useful stategy in the management of therapy.
慢性丙型肝炎在HIV阳性患者中常见且具有侵袭性，因此开发耐受性良好的丙型肝炎治疗方法是当务之急。我们评估了聚乙二醇化干扰素α2b（PEG-IFN）联合利巴韦林（RBV）与PEG-IFN单药治疗在接受高效抗逆转录病毒治疗（HAART）的HIV/HCV合并感染患者中的疗效和安全性，并分析了反应的预测因素。
一项意大利多中心开放标签试验，纳入135例合并感染患者，随机分为PEG-IFN 1.5μg/kg/周联合RBV 400mg每日2次（n = 69，A组）或PEG-IFN 1.5μg/kg/周（n = 66，B组），治疗48周。我们评估了第8周时早期病毒学反应（EVR，HCV-RNA较基线下降>2 log10或检测不到）对持续病毒学反应（SVR）的预测价值。
55例患者（A组28例，B组27例）完成了48周治疗。治疗结束时，A组28例患者中有20例、B组27例患者中有11例HCV-RNA<50 IU/ml。在符合方案分析中，A组54%的患者达到SVR（2-3基因型，11/16；1-4基因型，4/12），B组为22%（2-3基因型，3/15；1-4基因型，3/12）。在意向性分析中，A组SVR为22%（2-3基因型，11/32；1-4基因型，4/37），B组为9%（2-3基因型，3/32；1-4基因型，3/34）。SVR的最佳预测因素是联合治疗的使用、HCV 3基因型感染与1基因型感染以及第8周的EVR。30例患者（A组15例，B组15例）因副作用提前退出试验。第8周时EVR的阳性预测值为65%，阴性预测值为86%。
PEG-IFN联合RBV可被视为治疗HIV/HCV合并感染患者的可靠选择。成功提高疗效的关键是通过严格的整体患者监测实现高度依从性，以便最佳管理药物毒性。第8周的EVR评估可能成为治疗管理中的有用策略。
